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Browsing by Subject "Ketogenic diet"
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Item Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study(BMJ Publishing Group, 2019-02-25) Vilar-Gomez, Eduardo; Athinarayanan, Shaminie J.; Adams, Rebecca N.; Hallberg, Sarah J.; Bhanpuri, Nasir H.; McKenzie, Amy L.; Campbell, Wayne W.; McCarter, James P.; Phinney, Stephen D.; Volek, Jeff S.; Chalasani, Naga; Medicine, School of MedicineOBJECTIVE: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS: At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). CONCLUSIONS: One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D.Item Reply to "Utility of Unrefined Carbohydrates in Type 2 Diabetes. Comment on Reversing Type 2 Diabetes: A Narrative Review of the Evidence, Nutrients, 2019, 11, 766"(MDPI, 2019-07-18) Hallberg, Sarah J.; Gershuni, Victoria M.; Hazbun, Tamara L.; Athinarayanan, Shaminie J.; Medicine, School of MedicineWe appreciate the interest and comments from Joshi et al. [1] regarding our recent paper [2]. Here are our specific comments to concerns that they raised.Item The role of pyruvate dehydrogenase kinase in glucose and ketone body metabolism(2012-07) Rahimi, Yasmeen; Harris, Robert A. (Robert Allison), 1939-; Considine, Robert V.; Roach, Peter J.; Wek, Ronald C.The expression of pyruvate dehydrogenase kinase (PDK) 2 and 4 are increased in the fasted state to inactivate the pyruvate dehydrogenase complex (PDC) by phosphorylation to conserve substrates for glucose production. To assess the importance of PDK2 and PDK4 in regulation of the PDC to maintain glucose homeostasis, PDK2 knockout (KO), PDK4 KO, and PDK2/PDK4 double knockout (DKO) mice were generated. PDK2 deficiency caused higher PDC activity and lower blood glucose levels in the fed state while PDK4 deficiency caused similar effects in the fasting state. DKO intensified these effects in both states. PDK2 deficiency had no effect on glucose tolerance, PDK4 deficiency produced a modest effect, but DKO caused a marked improvement, lowered insulin levels, and increased insulin sensitivity. However, the DKO mice were more sensitive than wild-type mice to long term fasting, succumbing to hypoglycemia, ketoacidosis, and hypothermia. Stable isotope flux analysis indicated that hypoglycemia was due to a reduced rate of gluconeogenesis. We hypothesized that hyperglycemia would be prevented in DKO mice fed a high saturated fat diet for 30 weeks. As expected, DKO mice fed a high fat diet had improved glucose tolerance, decreased adiposity, and were euglycemic due to reduction in the rate of gluconeogenesis. Like chow fed DKO mice, high fat fed DKO mice were unusually sensitive to fasting because of ketoacidosis and hypothermia. PDK deficiency resulted in greater PDC activity which limited the availability of pyruvate for oxaloacetate synthesis. Low oxaloacetate resulted in overproduction of ketone bodies by the liver and inhibition of ketone body and fatty acid oxidation by peripheral tissues, culminating in ketoacidosis and hypothermia. Furthermore, when fed a ketogenic diet consisting of low carbohydrate and high fat, DKO mice also exhibited hypothermia, ketoacidosis, and hypoglycemia. The findings establish that PDK2 is more important in the fed state, PDK4 is more important in the fasted state, survival during long term fasting depends upon regulation of the PDC by both PDK2 and PDK4, and that the PDKs are important for the regulation of glucose and ketone body metabolism.